This application proposes to continue and expand our efforts to establish a center for the basic biology of aging at the Medical College of Pennsylvania and Hahnemann University. The overall goal is to support and catalyze high quality research on the basic biology of aging by establishing cores which will facilitate research in a cost effective way as well as provide a focal point for collaborative research. The title of our proposed program "Dysregulation During Aging: Molecules, Cells and Tissues" reflects our research strengths and interests at this institution as well the goals of the RFA, i.e. to enhance the ability of investigators to acquire fundamental knowledge about the mechanisms of aging. This proposal addresses the establishment of shared core resources to achieve maximum impact and avoid the costliness of duplication, the provision of start-up funds for investigators new to aging, mentoring of new investigators and ongoing access to the "cutting edge" of this field through seminars, symposia and workshops. To this end we have proposed to establish five cores: an Animal Core for mice and rats; a Cell and Tissue Core; a Brain Bank Core; a Research Development Core and a Program Enrichment Core. We have chosen three overlapping, interactive themes: changes in excitable tissues during aging; the regulation of gene expression during aging and the biological mechanisms of immunosenescence. These represent the strengths and interests of the faculty at this institution. The Animal Core proposes the expansion of our aging animal facility for the study of male/female differences in aging. The Cell and Tissue Core resource will consist of a cell bank, an animal tissue bank with both "cryofixed" and "cryopreserved" specimens and a human tissue bank for storage of peripheral blood cells and sera of different age individuals. The Brain Bank Core will provide brain tissue and neuropathology diagnostic services. Based on autopsy records from AHERF hospitals we anticipate about 80 brains per year from individuals without dementing illness. The Research Development Core proposes to identify outstanding investigators interested in aging and to guide them through the initial stages of their research careers. Finally, the Program Enrichment Core will provide support for all administrative aspects of the center.